Optimizing of 2,3-diarylindenes as fluorescent estrogens: Variation of the acceptor group, ortho substitution of the 2-ring, and C-1 methylation

Gregory M Anstead, John A. Katzenellenbogen

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Abstract

In an attempt to elucidate steric and electronic factors that affect the fluorescence and estrogen receptor binding properties of 2,3-diarylindenes, we have prepared and examined the behavior of 11 analogues bearing substituents on the 1-position or on the 2-aryl ring. These compounds were synthesized by alkylation of a 1,2-diarylethanone with 3-methoxybenzyl chloride, followed by cyclodehydration to the indene. The electronic spectra of those compounds without π-electron accepting groups on the 2-aryl ring display the absorbance and fluorescence of a hindered stilbene system; those with nitro and cyano substituents on the 2-aryl ring show charge-transfer character, having a more bathochromic absorption and fluorescence. One bisphenolic nitroindene, in particular, shows a strong, long-wavelength absorption and an intense emission, with a large Stokes' shift that is highly sensitive to solvent polarity. Estrogen receptor binding affinity measurements on these compounds indicate that substituents that twist the pendant aryl rings (such as a 1-methyl group, or an o-methyl or trifluoromethyl group on the 2-phenyl ring) increase binding affinity. Bulky (4-bromo) or electron-withdrawing groups (3- and 4-nitro, 4-cyano) on the 2-phenyl group, or its replacement with a 3-pyridyl group, greatly reduce binding affinity, suggesting that the complementary region of the receptor is relatively intolerant of bulk and may have specific hydrogen-bonding requirements. This investigation of the concurrent effects of substituents on the fluorescence properties and receptor binding affinity of 2,3-diarylindenes should assist in the development of effective, inherently fluorescent ligands for the estrogen receptor.

Original languageEnglish (US)
Pages (from-to)1754-1761
Number of pages8
JournalJournal of Medicinal Chemistry
Volume31
Issue number9
StatePublished - 1988
Externally publishedYes

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Methylation
Estrogens
Substitution reactions
Fluorescence
Estrogen Receptors
Bearings (structural)
Electrons
Stilbenes
Alkylation
Hydrogen Bonding
Intermetallics
Charge transfer
Chlorides
Hydrogen bonds
Ligands
Wavelength

ASJC Scopus subject areas

  • Organic Chemistry

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Optimizing of 2,3-diarylindenes as fluorescent estrogens : Variation of the acceptor group, ortho substitution of the 2-ring, and C-1 methylation. / Anstead, Gregory M; Katzenellenbogen, John A.

In: Journal of Medicinal Chemistry, Vol. 31, No. 9, 1988, p. 1754-1761.

Research output: Contribution to journalArticle

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